The presentation and natural history of immunodeficiency caused by nuclear factor κB essential modulator mutation
The presentation and natural history of immunodeficiency caused by nuclear factor κB essential modulator mutation
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DOI：
10.1016/j.jaci.2004.01.762
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发表时间：
2004-04-01
影响因子：
14.2
通讯作者：
Bonilla, FA
中科院分区：
文献类型：
--
作者：
Orange, JS;Jain, A;Bonilla, FA
背景资料：越来越多的罕见遗传缺陷与免疫缺陷和通过核因子（NF）κ B激活基因转录的能力受损有关。NF κ B必需调节因子（NEMO）的亚型突变损害NF κ B的功能，并与免疫缺陷和外胚层发育不良（艾德）以及对非典型分枝杆菌感染的易感性有关。目的：我们试图研究NEMO突变伴免疫缺陷（NEMO-ID）患者的临床和免疫学自然史。对严重细菌感染和艾德或原因不明的分枝杆菌敏感性患者进行NEMO突变评估。结果：7例患儿确诊为NEMO-ID，其中6例为艾德，5例NEMO基因第10外显子突变。我们得出的NEMO-ID的估计发病率为1：250，000活产男婴。所有患者在生命早期都患有严重的化脓性细菌疾病，首次感染的中位年龄为8.1个月。大多数男孩患有分枝杆菌病（中位年龄为84个月），少数患有疱疹病毒感染。初始免疫学评估显示低丙种球蛋白血症（中位IgG，170 mg/dL）伴可变IgM（中位41 mg/dL）和IgA（中位143 mg/dL）水平。2例患者IgM水平升高，5例患者IgA水平升高。所有接受评估的患者淋巴细胞亚群正常，增殖反应、特异性抗体产生和自然杀伤细胞功能受损。2例患者死于分枝杆菌病并发症（年龄21和33个月）。结论：NEMO-ID是一种联合免疫缺陷，早期易患化脓性细菌，后期易患分枝杆菌感染。这些患者中特定NEMO突变的具体特征提供了对该基因在免疫功能中的作用的深入了解。
Background: An increasing number of rare genetic defects are associated with immunodeficiency and impaired ability to activate gene transcription through nuclear factor (NF) kappaB. Hypomorphic mutations in the NFkappaB essential modulator (NEMO) impair NFkappaB function and are linked to both immunodeficiency and ectodermal dysplasia (ED), as well as susceptibility to atypical mycobacterial infections.Objective: We sought to investigate the clinical and immunologic natural history of patients with NEMO mutation with immunodeficiency (NEMO-ID).Methods: Patients with severe bacterial infection and ED or unexplained mycobacterial sensitivity were evaluated for NEMO mutation. Laboratory investigations and clinical data were retrospectively and prospectively accumulated and reviewed.Results: We have given a diagnosis of NEMO-ID to 7 boys; 6 had ED, and 5 had gene mutations in the 10th exon of NEMO. Our resulting estimated incidence of NEMO-ID is 1:250,000 live male births. All patients had serious pyogenic bacterial illnesses early in life, and the median age of first infection was 8.1 months. Most boys had mycobacterial disease (median age, 84 months), and a minority had herpesviral infections. Initial immunologic assessments showed hypogammaglobulinemia (median IgG, 170 mg/dL) with variable IgM (median, 41 mg/dL) and IgA (median, 143 mg/dL) levels. Two patients had increased IgM levels, and 5 had increased IgA levels. All patients evaluated had normal lymphocyte subsets with impaired proliferative responses, specific antibody production, and natural killer cell function. Two patients died from complications of mycobacterial disease (ages 21 and 33 months).Conclusion: NEMO-ID is a combined immunodeficiency with early susceptibility to pyogenic bacteria and later susceptibility to mycobacterial infection. Specific features of particular NEMO mutations in these patients provide insight into the role of this gene in immune function.